Studies are proposed to study the incorporation of drugs of abuse into human hair in order to better understand the mechanisms involved and factors effecting drug incorporation into hair. In a series of experiments, controlled doses of three deuterium-labeled drugs of abuse (cocaine, methamphetamine, and morphine) will be administered. Sequential plasma, urine, sweat, and hair samples will be collected, then analyzed by GC/MS. The pharmacokinetics of the drugs in biological fluids will be compared with drug uptake into hair. Specific objectives of the program will be to determine: 1) the relationship between the amount of drug used and the concentration of drug and metabolites in plasma, urine, sweat, and hair; 2) the reliability of segmental analysis, i.e., the relationship between the time of drug use and the position of drug along the hair shaft and the time interval between drug use and appearance of drug in hair; 3) the minimum dose required to produce a positive result in hair; 4) in situ stability of drugs in hair, i.e., how long hair will remain positive; 5) how factors such as sex, age, race and hair type effect drug incorporation and retention. One important component of this program will be to test the hypothesis that "sweat and sebaceous gland secretions play a significant role in the incorporation of drugs into hair". In addition, a pilot program will be undertaken to evaluate whether there are sufficient concentrations of cocaethylene incorporated into hair to be useful as an indicator of combined alcohol cocaine use. Unique features of these proposed studies include: 1) administration of precise doses in a controlled clinical setting, 2) quantitation of drug by GC/MS, and 3) the use of isotope-labeled drug to control for residual stores of the drug in the body and surreptitious drug use by subjects during the study. Studies will be conducted at the School of Medicine, University of California, Davis and the Langley Porter Institute, University of California, San Francisco. Systematic studies like the ones proposed might provide the necessary scientific underpinning for hair analysis to be used routinely as a biomarker for exposure to drugs and chemicals.